045 Optical imaging of lung cancer using near-infrared fluorescence

Abstract

Introduction We report here the in vitro and in vivo characteristics of a new molecular conjugate vector for targeting and imaging of tumors. Its core is a cyclo-decapeptide plateform named RAFT, onto which two spatially independent functional domains can be cova-lently and stereo-specifically linked : a cell targeting domain for tumor targeting and a labeling domain able to carry two drugs and/or labeling agent. In order to prove the interest of this carrier, we used a well known cRGD cyclopeptide, a ligand for the α v β 3 integrin. Methods Using competition assays and confocal microscopy in vitro , as well as in vivo tumor formation and near-infrared optical imaging in mice, we analyzed the characteristics of the RAFT(cRGD)4 vector. Results We demonstrate that this vector presenting 4 cRGD motifs very efficiently prevents (α v β 3 -mediated cell adhesion to vit-ronectin. Furthermore, it is actively endocytosed because of the multivalent cRGD presentation, a major advantage for drug delivery. In vivo experiments in nude mice reveal that repeated intratu-moral injections of low doses of RAFT(cRGD)4 reduce tumor growth by reducing the number of tumor blood vessels. Furthermore, RAFT(cRGD)4 significantly improves the targeting specifi-city of subcutaneous tumor masses as well as disseminated metastasis after intravenous injection. Conclusion Thus, RAFT (cRGD)4 is specific, internalized, perfectly controlled and can carry multiple biological functions on a single, spatially defined backbone, making of it a powerful and versatile synthetic vector for drug delivery, molecular imaging or both. This versatility is a major advantage since we can load it with multiple functions. This was demonstrated by the addition of a cytotoxic KL peptide on the cargo domain of the RAFT. RAFT-RGD-KL shows a very promissing specific antitumoral activity when injected intravenously in tumors bearing mice. Finally, recent developments in the optical System allowed us to follow these optical probes using a new 3D optical tomographic system in lung metastasis. This allowed us to detect lung metastasis in 3D for the first time to our knowledge using optical NIR probes.